Development of a Pilot Scale Process for the Anti-Alzheimer Drug (−)-Galanthamine Using Large-Scale Phenolic Oxidative Coupling and Crystallisation-Induced Chiral Conversion

1999/11/01 by B. Kuenburg, L. Czollner, Johannes Fröhlich +1 · 3 citations
Chemistry · Pharmacology, Toxicology and Pharmaceutics · Medicine · #Chemical synthesis and alkaloids #Alkaloids: synthesis and pharmacology #Cholinesterase and Neurodegenerative Diseases

paper · doi:10.1021/op990019q

openalex publication_date 1999/11/01 · openalex created_date 2025/10/10 · openalex updated_date 2026/07/07

Abstract

(−)-Galanthamine has been synthesised using an efficient nine-step procedure, which in large scale affords 12.4 (6.7−19.1)% overall yield. The process improvements and optimization of each step are described. Notable steps include (i) an oxidative phenol coupling and (ii) crystallisation-induced chiral conversion of (±)-narwedine to (−)-narwedine. This is a practical and cost-effective synthesis of (−)-galanthamine which is amenable to pilot plant scale-up to afford sufficient material for use in clinical trials.

Citations

• Asymmetric Transformation of Either Enantiomer of Narwedine via Total Spontaneous Resolution Process, a Concise Solution to the Synthesis of (-)-Galanthamine

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